The major objective of this project is the achievement of chemical enhancement of radiation injury to experimental tumors of the nervous system in rats. The first experimental model consists of tumors growing in vivo after injections of cultured tumor cells into the host brain. For young rats inoculation has been accomplished by a free-hand method. For older rats, a stereotaxic method is being developed for accurate placement and for use of either tumor size or survival time as end point. The cells are derived from a series of clones and cell lines grown from primary ethyl-nitrosourea induced central nervous system tumors, including astrocytoma, spongioblastoma, mixed gliomas, undifferentiated glioma, and Schwannoma. Agents to be used on this model in combination with x-irradiation include lysosomal labilizers and membrane altering compounds (Vitamin A, Filipin), high electron affinity compounds (nitroheterocyclic compounds), agents such as cyclophosphamide which are promising for non-nervous system tumors and are needed for standardization purposes. The second model is an in vitro system dealing with the culture of the cell lines and clones exposure to x-irradiation and measurement of survival by colony formation. This system will be used as a more precise index of direct effect of agents on tumor cells and for elimination of systemic toxicity and tumor penetration problems of in vivo model.